276 BrainResearcJ~,{O~ (1986)276-287 Elsevier BRE 12194 Glutamate Receptor Agonists Release [3H]GABA Preferentially From Horizontal Cells JULIO MORAN I, HERMINIA PASANTES-MORALES2 and DIANNA A. REDBURN ~ t Department of Neurobiology and Anatomy, University of Texas Medical School at Houston, Houston, TX 77025 ( U.S.A. ) and eCentro de lnvestigaciones en Fisiologia Celula, Universidad Nacional Autonoma de Mexico, Mexico (Mexico) (Accepted 6 May 1986) Key words: Glutamate -- Aspartate- Kainic acid --),-Aminobutyric acid (GABA) -- Retina A total of 5-6 different cell types in vertebrate retinas accumulate [3H])~-aminobutyricacid (GABA). In frog retina, specific pop- ulations of ceils in the horizontal, amacrine and ganglion cell layers are labeled autoradiographically after a 15-min in vitro incubation with [3H]GABA. Cells which may be bipolar or interplexiform cells are also labeled. Similar autoradiographic patterns are observed in chick retina except for the absence of labeled bipolar or interptexiform cells. In rat retinas, [3H]GABA uptake is limited primarily to Muller and amacrine cells. Depolarizing glutamate receptor agonists (glutamate, aspartate and kainic acid) applied in an in vitro per- fusion system, stimulated massive release of [3H]GABA from frog and chick retina but not from rat retina.~Under these conditions, autoradiographic labeling of horizontal cells was virtually depleted, while labeling of other cell types remained robust. In contrast, po- tassium caused release of the label from all 3 types of retina, and loss of autoradiographic labeling occurred uniformly in all cell types. We conclude that [3H]GABA-accumulating horizontal cells possess depolarizing glutamate receptors and that activation of these re- ceptors leads to a release of GABA stores. On the other hand, Muller cells and the various subclasses of [3H]GABA-accumulating am- acrine, bipolar and/or interplexiform cells, do not release GABA in response to glutamate receptor stimulation and thus appear to be relatively insensitive to excitatory amino acids. INTRODUCTION There is a large body of evidence which suggests that amino acids play a major role in chemical trans- mission in the retina j. Glutamate and/or aspartate (Glu/Asp) are principal candidates for the neuro- transmitter(s) released from photoreceptor cells and from some classes of bipolar cells 9'23"25"26"31. These cells represent first and second order neurons respec- tively within the visual pathway of the retina. Vari- ous second and third order retinal neurons show dif- ferent responses to Glu/Asp input, as a result of dif- ferent types of Glu/Asp receptors have been pos- tulated, based on their pharmacological sensitivity and electrophysiological responses 2'4"14'24. All of these receptors are sensitive to glutamate and aspar- tate; nevertheless, they can be distinguished on the basis of their relative affinities for 4 Glu/Asp ana- logues namely N-methyl-D-aspartate (NMDA), quisqualate (QA), kainate (KA), or 2-amino-4-phos, phonobutyrate (APB). The APB type of Glu/Asp re- ceptor displays a unique characteristic in that it causes hyperpolarization and it is probably limited in its retinal distribution to 'ON' depolarizing bipolar cells 24. The other three types of Glu/Asp receptors all lead to depolarization and their precise localization in retina is not as well established as the APB recep- tor3, 23,25" Gamma aminobutyric acid (GABA) is probably an inhibitory neurotransmitter utilized by some am- acrine cells in retina I'1s. In addition, horizontal cells and perhaps bipolar cells or interplexiform cells in re- tinas from nonmammalian vertebrates are probably GABAergic 2~-3°'32. These GABAergic cells repre- sent secondary and tertiary cells in the retina. The relative position of the Glu/Asp releasing cells with respect to the GABAergic cells within the visual pathway, suggests that the release of GABA might be stimulated directly or indirectly by activation of depolarizing Glu/Asp receptors. Correspondence: D.A. Redburn, Department of Neurobiology and Anatomy, University of Texas Medical School at Houston, P.O. Box 20708, Houston, TX 77025, U.S.A. 0006-8993/86/$03.50 © 1986 Elsevier Science Publishers B.V. (Biomedical Division)